Differences in Mycoplasma arthritidis-induced arthritis in rats, mice and rabbits provide an opportunity to examine the influence of host factors on arthritis pathogenesis. Rats develop an acute, self-limited arthritis, while the disease in mice and rabbits in chronic and long-lasting. Disease in rats and mice is associated with an active infectious process, while in rabbits, which eliminate viable organisms very early, it appears to be immunologically-mediated. The failure of rats and mice to express metabolic-inhibition (MI) antibodies (usually considered protective) against M. arthritidis suggests that they are unable to respond to major membrane antigens. We will examine the ability of rat and mouse, compared to rabbit, antisera to react with M. arthritidis membrane antigens using 1) a combination of immunoprecipitation of immune complexes formed by these antisera and 125-I-labeled membrane antigens, polyacrylamide gel electrophoresis and autoradiography and 2) an enzyme-linked immunosorbent assay, and we will determine whether lack of antigenic recognition is due to a heterogenetic antigen or to selective immunosuppression by M. arthritidis. We also hope to determine whether antigenic differences among M. arthritidis strains are related to virulence, and whether the ability of different animals to recognize major membrane antigens is related to their susceptibility to arthritis. In addition, we will attempt to identify the humoral protective factor found in convalescent rat serum and the mycoplasmal component against which it is directed. Rabbits produce a highly active immune response against M. arthritidis and the disease may be immune complex-mediated. We hope to determine whether a mycoplasmal or host-derived antigen participates in these complexes and to define their role in pathogenesis. We will use techniques designed to elute complexes from tissues, along with challenge of immunized and previously infected rabbits with viable and nonviable mycoplasmas dor this purpose. Altogether, we expect to gain considerable insight into mechanisms of chronic inflammatory joint diseases, which sould have considerable relevance in terms of human arthritis.